2023 Project 7

From Embryology
Student Projects 2023: 1 Patterning neural border and NC | 2 NPB NEUcrest | 3 EMT and NC | 4 miRNA and NC | 5 Adrenal Gland and NC | 6 Melanocyte & Melanoma | 7 Neurocristopathies | Neural Crest
These projects are the sole work of undergraduate science students and may contain errors in fact or descriptions.


Since the NC generates so many tissues/cell types in the adult body, and the signals that lead to its correct development have to be strictly regulated, it is not surprising that a vast number of genetic diseases are due to a defect of migration, differentiation survival proliferation of these cells. Such diseases are globally called neurocristopathies (NCPs). Several genes have been associated with NCPs, many of these with a well established role in NC development. But, because of the variety of diseases and the complexity of the NC gene regulatory network, not all of the genes involved in NCPs have been discovered yet.[1][2] According to the gene (or genes) involved, and the stage at which the defects arise, they can affect one or more tissues/cell types.

Examples of Different Neurocristopathies

Craniosynostosis is a condition that arises when two (or more) bones of the skull fuse prematurely during development. This condition, more than causing craniofacial abnormalities, does not give enough room for the brain to grow and, if not surgically treated, can cause intellectual disability. Many genes have been implicated in this heterogeneous condition, and not all of them have been yet discovered.[3]

CHARGE syndrome is a rare disease mainly caused by mutations in the CHD7 gene. The characteristics of this syndrome include coloboma of the eye, heart defects, atresia of the choanae, retardation, genital and ear abnormalities (which give the name to the syndrome). Not all of these signs are present among all CHARGE patients, denoting the complexity of this syndrome.[4] DiGeorge Syndrome (or 22q11 deletion syndrome) is characterised by a spectrum of problems that range from learning disabilities, speech and hearing problems, heart defects and cleft palate. It results from deletion of a portion of the long arm of Chromosome 22 (which gives the name to the disease). An important gene affected by this deletion is TBX1, an important gene for the embryonic development of pharyngeal pouches.[5]

Melanoma is a type of skin cancer that begins in melanocytes and can affect people of every age. Is one of the most common cancers and is mainly triggered by excessive exposure to sunlight. However, genetic factors can facilitate the onset of this disease.[6] Neuroblastoma is one of the most common and aggressive cancer in child. It arises from the sympathoadrenal lineage derived from trunk NCC, and among the genetic causes, there are mutations in ALK, MYCN and PHOX2B.[7]

WS is a condition characterised by hearing loss and pigmentation abnormalities of the skin, iris and hair. Divided in four types, they are differentiated globally by dystopia canthorum (DC);  absence of DC; abnormalities of upper limbs; and Hirschsprung disease respectively. Most of WS patients bear mutations on PAX3, MITF and SOX10 gene and a minority on EDNRB, EDN3 and KITLG gene. Despite very heterogeneous, type 2 has less than 50% of molecularly explained cases.  As for most of the NCPs, not all the genetic causes have been discovered yet.[8][9]

These are only examples of diseases that can arise from NC developmental defects, but the list is longer, and the tissues/cell types implicated are many. At the moment, many efforts are being made by several laboratories around the globe in order to identify all the genetic causes underlying the onset of NCPs and, eventually, to provide better prognosis and genetic counselling for the patients and their families.


  1. Vega-Lopez GA, Cerrizuela S, Tribulo C & Aybar MJ. (2018). Neurocristopathies: New insights 150 years after the neural crest discovery. Dev. Biol. , , . PMID: 29802835 DOI.
  2. Sato TS, Handa A, Priya S, Watal P, Becker RM & Sato Y. (2019). Neurocristopathies: Enigmatic Appearances of Neural Crest Cell-derived Abnormalities. Radiographics , 39, 2085-2102. PMID: 31697622 DOI.
  3. Goos JAC & Mathijssen IMJ. (2019). Genetic Causes of Craniosynostosis: An Update. Mol Syndromol , 10, 6-23. PMID: 30976276 DOI.
  4. Usman N & Sur M. (2023). CHARGE Syndrome. , , . PMID: 32644625
  5. Lackey AE & Muzio MR. (2023). DiGeorge Syndrome. , , . PMID: 31747205
  6. Rastrelli M, Tropea S, Rossi CR & Alaibac M. (2014). Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo , 28, 1005-11. PMID: 25398793
  7. Wulf AM, Moreno MM, Paka C, Rampasekova A & Liu KJ. (2021). Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer. Int J Mol Sci , 22, . PMID: 34769149 DOI.
  8. Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S & Bondurand N. (2010). Review and update of mutations causing Waardenburg syndrome. Hum Mutat , 31, 391-406. PMID: 20127975 DOI.
  9. Huang S, Song J, He C, Cai X, Yuan K, Mei L & Feng Y. (2022). Genetic insights, disease mechanisms, and biological therapeutics for Waardenburg syndrome. Gene Ther , 29, 479-497. PMID: 33633356 DOI.